Field of the Invention
The present invention generally relates to phenethyldihydrobenzodioxolone compounds and compositions useful for reducing or inhibiting tumor growth. It also relates to methods of use and the preparation of phenethyldihydrobenzodioxolone compounds.
Description of the Related Art
Medicines used by oncologists to treat the majority of solid tumors and various other cancers have not significantly changed in the last twenty years. In fact, nitrogen mustards, antifolates, platinums, nucleoside analogues, taxanes, and anthracyclines are all still first-line or primary therapies despite record increases in R&D spending by the NIH and the pharmaceutical industry. Furthermore, large scale genomics efforts have yielded results that have contradicted expectations of a future full of targeted therapies. For the majority of solid tumors, targeted therapies must still be given along with more traditional non-selective chemotherapies. Thus, there is a need for new chemotherapeutic agents for use as both monotherapies and for combination with new targeted therapies.
The taxanes and vinca alkaloids are first-line chemotherapies that have robustly proven the superior benefits of inhibiting microtubules for increasing overall survival of patients with advanced stage cancer. Newer microtubule inhibitors have further demonstrated the clinical superiority of microtubule inhibitors in breast, prostate, and ovarian cancers and lymphoma. Microtubule inhibitors have withstood dozens of head to head competitive clinical trials unequivocally demonstrating that this is a preferred mechanism of action for antitumor agents.
The identification of a new microtubule inhibitor, bifidenone, is reported in patent application Ser. No. 14/851,624, filed Sep. 11, 2015, entitled “Bifidenone Compositions and Methods of Use” incorporated herein in its entirety. Bifidenone has a phenethyldihydrobenzodioxolone (“7,7a-dihydro-7a-phenethylbenzo[d][1,3]dioxol-5(6H)-one”) scaffold and inhibits tubulin polymerization. The present invention provides analogues of phenethyldihydrobenzodioxolone compounds.